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Gene Review

Srebf1  -  sterol regulatory element binding...

Mus musculus

Synonyms: ADD-1, ADD1, D630008H06, SREBP-1, SREBP-1a, ...
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Disease relevance of Srebf1


High impact information on Srebf1

  • However, unlike SREBP itself, PGC-1beta reduces fat accumulation in the liver while greatly increasing circulating triglycerides and cholesterol in VLDL particles [4].
  • Further, PGC-1beta is required for SREBP-mediated lipogenic gene expression [4].
  • Transcription factors in the sterol responsive element binding protein (SREBP) family are key regulators of the lipogenic genes in the liver [4].
  • The transcriptional increase in SREBP-1c mRNA by RXR/LXR was accompanied by a similar increase in the level of the nuclear, active form of the SREBP-1c protein and an increase in fatty acid synthesis [5].
  • Expression of the related gene products, SREBP-1a and SREBP-2, were not increased [5].

Chemical compound and disease context of Srebf1


Biological context of Srebf1


Anatomical context of Srebf1


Associations of Srebf1 with chemical compounds

  • Because this active form of SREBP-1c controls the transcription of genes involved in fatty acid biosynthesis, our results reveal a unique regulatory interplay between cholesterol and fatty acid metabolism [5].
  • In this report, we describe a novel LXR target, the sterol regulatory element-binding protein-1c gene (SREBP-1c), which encodes a membrane-bound transcription factor of the basic helix-loop-helix-leucine zipper family [5].
  • We have produced transgenic mice whose livers express a dominant positive NH2-terminal fragment of sterol regulatory element binding protein-1c (SREBP-1c) [10].
  • We have previously shown that the disruption of SREBP-1 in ob/ob mice decreased their liver triglyceride storage [11].
  • The SREBP-1c isoform is a known mediator of insulin action on hepatic gene expression, but its transcriptional effects due to glucose or fructose are still unclear [18].
  • We also show similar cooperative activation of the mitochondrial glycerol-3-phosphate acyltransferase promoter by USF and SREBP-1c [19].
  • Taken together, these studies reveal that there are alternative molecular mechanisms for activating SREBP target genes in response to the different dietary challenges of Zetia/lovastatin versus fasting/refeeding [20].

Physical interactions of Srebf1


Regulatory relationships of Srebf1

  • Down-regulation of SREBP-1 expression with the specific small interfering RNA blocked basal and LXRbeta-induced expression of pancreatic duodenal homeobox 1 (PDX-1), insulin, and Glut2 genes [16].
  • These results demonstrate that SREBP-2 appears to promote adipocyte differentiation as well as SREBP-1 and that the proteolytic activation of SREBPs may be induced by an as-yet unidentified mechanism in lipid loaded adipocytes [26].
  • While the PUFA/cholesterol (PUFA/CH) diets repressed the maturation of the SREBP-1, the SCD1 mRNA levels, and protein and enzyme activity were induced [27].
  • A role for PPARalpha in the control of SREBP activity and lipid synthesis in the liver [28].
  • The LXR-induced SREBP-1c precursor, however, is rapidly cleaved on acute exposure to insulin via a phosphatidylinositol 3-kinase-dependent mechanism [29].

Other interactions of Srebf1


Analytical, diagnostic and therapeutic context of Srebf1


  1. Absence of sterol regulatory element-binding protein-1 (SREBP-1) ameliorates fatty livers but not obesity or insulin resistance in Lep(ob)/Lep(ob) mice. Yahagi, N., Shimano, H., Hasty, A.H., Matsuzaka, T., Ide, T., Yoshikawa, T., Amemiya-Kudo, M., Tomita, S., Okazaki, H., Tamura, Y., Iizuka, Y., Ohashi, K., Osuga, J., Harada, K., Gotoda, T., Nagai, R., Ishibashi, S., Yamada, N. J. Biol. Chem. (2002) [Pubmed]
  2. Hepatic Akt activation induces marked hypoglycemia, hepatomegaly, and hypertriglyceridemia with sterol regulatory element binding protein involvement. Ono, H., Shimano, H., Katagiri, H., Yahagi, N., Sakoda, H., Onishi, Y., Anai, M., Ogihara, T., Fujishiro, M., Viana, A.Y., Fukushima, Y., Abe, M., Shojima, N., Kikuchi, M., Yamada, N., Oka, Y., Asano, T. Diabetes (2003) [Pubmed]
  3. Role of sterol regulatory element-binding protein 1 in regulation of renal lipid metabolism and glomerulosclerosis in diabetes mellitus. Sun, L., Halaihel, N., Zhang, W., Rogers, T., Levi, M. J. Biol. Chem. (2002) [Pubmed]
  4. Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP. Lin, J., Yang, R., Tarr, P.T., Wu, P.H., Handschin, C., Li, S., Yang, W., Pei, L., Uldry, M., Tontonoz, P., Newgard, C.B., Spiegelman, B.M. Cell (2005) [Pubmed]
  5. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Repa, J.J., Liang, G., Ou, J., Bashmakov, Y., Lobaccaro, J.M., Shimomura, I., Shan, B., Brown, M.S., Goldstein, J.L., Mangelsdorf, D.J. Genes Dev. (2000) [Pubmed]
  6. Altered metabolic responses to intermittent hypoxia in mice with partial deficiency of hypoxia-inducible factor-1alpha. Li, J., Bosch-Marce, M., Nanayakkara, A., Savransky, V., Fried, S.K., Semenza, G.L., Polotsky, V.Y. Physiol. Genomics (2006) [Pubmed]
  7. Hepatic farnesyl diphosphate synthase expression is suppressed by polyunsaturated fatty acids. Le Jossic-Corcos, C., Gonthier, C., Zaghini, I., Logette, E., Shechter, I., Bournot, P. Biochem. J. (2005) [Pubmed]
  8. Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein (SREBP). You, M., Fischer, M., Deeg, M.A., Crabb, D.W. J. Biol. Chem. (2002) [Pubmed]
  9. The HIV protease inhibitor indinavir impairs sterol regulatory element-binding protein-1 intranuclear localization, inhibits preadipocyte differentiation, and induces insulin resistance. Caron, M., Auclair, M., Vigouroux, C., Glorian, M., Forest, C., Capeau, J. Diabetes (2001) [Pubmed]
  10. Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells. Shimano, H., Horton, J.D., Shimomura, I., Hammer, R.E., Brown, M.S., Goldstein, J.L. J. Clin. Invest. (1997) [Pubmed]
  11. Polyunsaturated fatty acids ameliorate hepatic steatosis in obese mice by SREBP-1 suppression. Sekiya, M., Yahagi, N., Matsuzaka, T., Najima, Y., Nakakuki, M., Nagai, R., Ishibashi, S., Osuga, J., Yamada, N., Shimano, H. Hepatology (2003) [Pubmed]
  12. Insulin and sterol-regulatory element-binding protein-1c (SREBP-1C) regulation of gene expression in 3T3-L1 adipocytes. Identification of CCAAT/enhancer-binding protein beta as an SREBP-1C target. Le Lay, S., Lefrère, I., Trautwein, C., Dugail, I., Krief, S. J. Biol. Chem. (2002) [Pubmed]
  13. Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver. Park, S.W., Moon, Y.A., Horton, J.D. J. Biol. Chem. (2004) [Pubmed]
  14. Overexpression of sterol regulatory element-binding protein-1a in mouse adipose tissue produces adipocyte hypertrophy, increased fatty acid secretion, and fatty liver. Horton, J.D., Shimomura, I., Ikemoto, S., Bashmakov, Y., Hammer, R.E. J. Biol. Chem. (2003) [Pubmed]
  15. The gene encoding acyl-CoA-binding protein is subject to metabolic regulation by both sterol regulatory element-binding protein and peroxisome proliferator-activated receptor alpha in hepatocytes. Sandberg, M.B., Bloksgaard, M., Duran-Sandoval, D., Duval, C., Staels, B., Mandrup, S. J. Biol. Chem. (2005) [Pubmed]
  16. Sterol regulatory element-binding protein 1 mediates liver X receptor-beta-induced increases in insulin secretion and insulin messenger ribonucleic acid levels. Zitzer, H., Wente, W., Brenner, M.B., Sewing, S., Buschard, K., Gromada, J., Efanov, A.M. Endocrinology (2006) [Pubmed]
  17. Up-regulation of SREBP-1c and lipogenic genes in skeletal muscles after exercise training. Ikeda, S., Miyazaki, H., Nakatani, T., Kai, Y., Kamei, Y., Miura, S., Tsuboyama-Kasaoka, N., Ezaki, O. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  18. Stearoyl-CoA desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and -independent mechanisms. Miyazaki, M., Dobrzyn, A., Man, W.C., Chu, K., Sampath, H., Kim, H.J., Ntambi, J.M. J. Biol. Chem. (2004) [Pubmed]
  19. Direct interaction between USF and SREBP-1c mediates synergistic activation of the fatty-acid synthase promoter. Griffin, M.J., Wong, R.H., Pandya, N., Sul, H.S. J. Biol. Chem. (2007) [Pubmed]
  20. Selective binding of sterol regulatory element-binding protein isoforms and co-regulatory proteins to promoters for lipid metabolic genes in liver. Bennett, M.K., Seo, Y.K., Datta, S., Shin, D.J., Osborne, T.F. J. Biol. Chem. (2008) [Pubmed]
  21. Acetyl-coenzyme A synthetase is a lipogenic enzyme controlled by SREBP-1 and energy status. Sone, H., Shimano, H., Sakakura, Y., Inoue, N., Amemiya-Kudo, M., Yahagi, N., Osawa, M., Suzuki, H., Yokoo, T., Takahashi, A., Iida, K., Toyoshima, H., Iwama, A., Yamada, N. Am. J. Physiol. Endocrinol. Metab. (2002) [Pubmed]
  22. The Liver X Receptor (LXR) and Hepatic Lipogenesis: THE CARBOHYDRATE-RESPONSE ELEMENT-BINDING PROTEIN IS A TARGET GENE OF LXR. Cha, J.Y., Repa, J.J. J. Biol. Chem. (2007) [Pubmed]
  23. Interferon-gamma-induced regulation of peroxisome proliferator-activated receptor gamma and STATs in adipocytes. Waite, K.J., Floyd, Z.E., Arbour-Reily, P., Stephens, J.M. J. Biol. Chem. (2001) [Pubmed]
  24. Yin yang 1 protein negatively regulates high-density lipoprotein receptor gene transcription by disrupting binding of sterol regulatory element binding protein to the sterol regulatory element. Shea-Eaton, W., Lopez, D., McLean, M.P. Endocrinology (2001) [Pubmed]
  25. Effects of fish oil feeding and fasting on LXRalpha/RXRalpha binding to LXRE in the SREBP-1c promoter in mouse liver. Nakatani, T., Katsumata, A., Miura, S., Kamei, Y., Ezaki, O. Biochim. Biophys. Acta (2005) [Pubmed]
  26. Proteolytic activation of SREBPs during adipocyte differentiation. Inoue, J., Kumagai, H., Terada, T., Maeda, M., Shimizu, M., Sato, R. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  27. Dietary cholesterol opposes PUFA-mediated repression of the stearoyl-CoA desaturase-1 gene by SREBP-1 independent mechanism. Kim, H.J., Miyazaki, M., Ntambi, J.M. J. Lipid Res. (2002) [Pubmed]
  28. A role for PPARalpha in the control of SREBP activity and lipid synthesis in the liver. Knight, B.L., Hebbachi, A., Hauton, D., Brown, A.M., Wiggins, D., Patel, D.D., Gibbons, G.F. Biochem. J. (2005) [Pubmed]
  29. Distinct roles of insulin and liver X receptor in the induction and cleavage of sterol regulatory element-binding protein-1c. Hegarty, B.D., Bobard, A., Hainault, I., Ferré, P., Bossard, P., Foufelle, F. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  30. Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Horton, J.D., Shah, N.A., Warrington, J.A., Anderson, N.N., Park, S.W., Brown, M.S., Goldstein, J.L. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  31. Increased expression of the sterol regulatory element-binding protein-1 gene in insulin receptor substrate-2(-/-) mouse liver. Tobe, K., Suzuki, R., Aoyama, M., Yamauchi, T., Kamon, J., Kubota, N., Terauchi, Y., Matsui, J., Akanuma, Y., Kimura, S., Tanaka, J., Abe, M., Ohsumi, J., Nagai, R., Kadowaki, T. J. Biol. Chem. (2001) [Pubmed]
  32. Regulation of SREBP1c gene expression in skeletal muscle: role of retinoid X receptor/liver X receptor and forkhead-O1 transcription factor. Kamei, Y., Miura, S., Suganami, T., Akaike, F., Kanai, S., Sugita, S., Katsumata, A., Aburatani, H., Unterman, T.G., Ezaki, O., Ogawa, Y. Endocrinology (2008) [Pubmed]
  33. Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice. Li, J., Grigoryev, D.N., Ye, S.Q., Thorne, L., Schwartz, A.R., Smith, P.L., O'Donnell, C.P., Polotsky, V.Y. J. Appl. Physiol. (2005) [Pubmed]
  34. Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1. Kim, J.B., Sarraf, P., Wright, M., Yao, K.M., Mueller, E., Solanes, G., Lowell, B.B., Spiegelman, B.M. J. Clin. Invest. (1998) [Pubmed]
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